title: Synthesis and pharmacological evaluation of aminothiazolomorphinans at the mu and kappa opioid receptors.
abstract: Previous studies with aminothiazolomorphinans suggested that this class of opioid ligands may be useful as a potential pharmacotherapeutic to decrease drug abuse. Novel aminothiazole derivatives of cyclorphan were prepared to evaluate a series of aminothiazolomorphinans with varying pharmacological properties at the κ opioid receptor (KOR) and μ opioid receptor (MOR). This study was focused on exploring the regioisomeric analogs with the aminothiazole on the C-ring of the morphinan skeleton. Receptor binding and [(35)S]GTPγS binding assays were used to characterize the affinity and pharmacological properties of the aminothiazolomorphinans. Intracranial self-stimulation (ICSS) was used to compare the effects of a representative aminothiazolomorphinan with the morphinan mixed-KOR/MOR agonist butorphan (MCL-101) on brain-stimulation reward.
authors.affiliation: Alcohol & Drug Abuse Research Center, ‡Mailman Research Center, McLean Hospital, Harvard Medical School , 115 Mill Street, Belmont, Massachusetts 02478, United States.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Provencher
authors.forename: Anna W
authors.initials: AW
authors.lastname: Sromek
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Shayla
authors.initials: S
authors.lastname: Russell
authors.forename: Elena
authors.initials: E
authors.lastname: Chartoff
authors.forename: Brian I
authors.initials: BI
authors.lastname: Knapp
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009019:Morphinans; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013844:Thiazoles